Classification and external resources
|Detailed view of a neuromuscular junction:|
1. Presynaptic terminal
2. Chemical synapses are specialized junctions through which Neurons signal to each other and to non-neuronal cells such as those in Muscles or Glands Sarcolemma
3. The sarcolemma is the Cell membrane of a muscle cell It consists of a true cell membrane called the plasma membrane and an outer coat made up of a thin layer of polysaccharide Synaptic vesicle
4. In a Neuron, synaptic vesicles, also called neurotransmitter vesicles, store the various Neurotransmitters that are released during Calcium -regulated Nicotinic acetylcholine receptor
5. Structure Nicotinic receptors with a molecular mass of 290 kDa, are made up of five subunits arranged symmetrically around the central pore. Mitochondrion
emerg/325 -emergency, med/3260 -pregnancy, oph/263 -eye
Myasthenia gravis (literally "serious muscle-weakness"; from Greek μύς "muscle", ἀσθένεια "weakness", and Latin gravis "serious"; abbreviated MG) is a neuromuscular disease leading to fluctuating muscle weakness and fatiguability. In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings G00-G99 - Diseases of the Nervous system (G00-G09 Inflammatory diseases of the Central nervous system ( Bacterial meningitis The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Greek (el ελληνική γλώσσα or simply el ελληνικά — "Hellenic" is an Indo-European language, spoken today by 15-22 million people mainly Latin ( lingua Latīna, laˈtiːna is an Italic language, historically spoken in Latium and Ancient Rome. Neuromuscular disease is a very broad term that encompasses many Diseases and ailments that either directly via intrinsic Muscle pathology or indirectly via It is an autoimmune disorder, in which weakness is caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine. Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily An acetylcholine receptor (abbreviated AChR) is an Integral membrane protein that responds to the binding of the Neurotransmitter Acetylcholine A neuromuscular junction ( NMJ) is the Synapse or junction of the Axon terminal of a Motoneuron with the motor end plate, the See Chemical synapse for an introduction to concepts and terminology used in this article The Chemical compound acetylcholine (often abbreviated ACh) is a Neurotransmitter in both the Peripheral nervous system (PNS and Central Myasthenia is treated medically with cholinesterase inhibitors or immunosuppressants, and, in selected cases, thymectomy. An acetylcholinesterase inhibitor or anti-cholinesterase is a chemical that inhibits the Cholinesterase enzyme from breaking down Acetylcholine An immunosuppressant is a substance that performs Immunosuppression of the Immune system. A thymectomy is an operation to remove the Thymus gland. It usually results in remission of Myasthenia gravis with the help of medication including Steroids At 200-400 cases per million it is one of the less common autoimmune disorders. Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues 
The hallmark of myasthenia gravis is muscle weakness that increases during periods of activity and improves after periods of rest. Muscle weakness (or "lack of strength" is a direct term for the inability to exert force with one's Muscles to the degree that would be expected given the individual's Muscles that control eye and eyelid movement, facial expression, chewing, talking, and swallowing are especially susceptible. In Linguistics ( Articulatory phonetics) manner of articulation describes how the tongue lips and other speech organs are involved in making a sound make Swallowing, known scientifically as deglutition is the process in the human or animal body that makes something pass from the Mouth, to the Pharynx, into The muscles that control breathing and neck and limb movements can also be affected. Breathing takes Oxygen in and Carbon dioxide out of the body Aerobic Organisms require oxygen to create energy via respiration, in Often the physical examination is within normal limits. 
The onset of the disorder can be sudden or rapid. Often symptoms come and go over time. The diagnosis of myasthenia gravis may be delayed if the symptoms are subtle or variable.
In most cases, the first noticeable symptom is weakness of the eye muscles. In others, difficulty in swallowing and slurred speech may be the first signs. The degree of muscle weakness involved in MG varies greatly among patients, ranging from a localized form, limited to eye muscles (ocular myasthenia), to a severe or generalized form in which many muscles - sometimes including those that control breathing - are affected. Ocular myasthenia gravis (MG is a disease of the neuromuscular junction resulting in hallmark variability in muscle weakness and fatigability Symptoms, which vary in type and severity, may include asymmetrical ptosis (a drooping of one or both eyelids), diplopia (double vision) due to weakness of the muscles that control eye movements, unstable or waddling gait, weakness in arms, hands, fingers, legs, and neck, a change in facial expression, dysphagia (difficulty in swallowing), shortness of breath and dysarthria (impaired speech, often nasal due to weakness of the pharyngeal muscles). Ptosis is an abnormally low position (drooping of the upper Eyelid. An eyelid is a thin fold of skin that covers and protects an Eye. Diplopia, commonly known as double vision, is the simultaneous Perception of two images of a single object Dysphagia should not be confused with the similarly pronounced Dysphasia, a language disorder Dysarthria is a motor Speech disorder resulting from neurological injury, characterised by poor articulation (cf
In myasthenic crisis a paralysis of the respiratory muscles occurs, necessitating assisted ventilation to sustain life. Paralysed redirects here For other uses see xx Paralysed (disambiguation Paralysis is the complete loss of Muscle function In Medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing when patients cannot do so on their own In patients whose respiratory muscles are already weak, crises may be triggered by infection, fever, an adverse reaction to medication, or emotional stress.  Since the heart muscle is stimulated differently, it is never affected by MG. The cardiac muscle is a type of involuntary striated Muscle found in the walls of the Heart.
Myasthenia gravis is an autoimmune disease: it features antibodies directed against the body's own proteins. Autoimmune diseases arise from an overactive Immune response of the body against substances and tissues normally present in the body While in various similar diseases the disease has been linked to a cross-reaction with an infective agent, there is no known causative pathogen that could account for myasthenia. A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious There is a slight genetic predisposition: particular HLA types seem to predispose for MG (B8 and DR3 with DR1 more specific for ocular myasthenia). The human leukocyte antigen system ( HLA) is the name of the Major histocompatibility complex (MHC in humans Up to 75% of patients have an abnormality of the thymus; 25% have a thymoma, a tumor (either benign or malignant) of the thymus, and other abnormalities are frequently found. In Medicine ( Oncology) thymoma is a Tumor originating from the Thymus. In Human anatomy, the thymus is an organ located in the upper Anterior portion of the chest cavity just behind the Sternum. The disease process generally remains stationary after thymectomy (removal of the thymus).
In MG, the autoantibodies are directed most commonly against the acetylcholine receptor (nicotinic type), the receptor in the motor end plate for the neurotransmitter acetylcholine that stimulates muscular contraction. An acetylcholine receptor (abbreviated AChR) is an Integral membrane protein that responds to the binding of the Neurotransmitter Acetylcholine Structure Nicotinic receptors with a molecular mass of 290 kDa, are made up of five subunits arranged symmetrically around the central pore. In Biochemistry, a receptor is a Protein molecule embedded in either the Plasma membrane or Cytoplasm of a cell to which a mobile signaling A neuromuscular junction ( NMJ) is the Synapse or junction of the Axon terminal of a Motoneuron with the motor end plate, the See Chemical synapse for an introduction to concepts and terminology used in this article The Chemical compound acetylcholine (often abbreviated ACh) is a Neurotransmitter in both the Peripheral nervous system (PNS and Central Some forms of the antibody impair the ability of acetylcholine to bind to receptors. Others lead to the destruction of receptors, either by complement fixation or by inducing the muscle cell to eliminate the receptors through endocytosis. The complement system is a Biochemical cascade that helps clear Pathogens from an organism Endocytosis is a process where cells absorb material ( Molecules such as proteins from the outside by engulfing it with their Cell membrane.
The antibodies are produced by plasma cells, that have been derived from B cells. These plasma cells are activated by T-helper cells, which in turn are activated by binding to acetylcholine receptor antigenic peptide sequences (epitopes) that rest within the histocompatibility antigens of antigen presenting cells. The thymus plays an important role in the development of T-cells, which is why myasthenia gravis is associated with thymoma. The exact mechanisms are however not convincingly clarified.
In normal muscle contraction, cumulative activation of the ACh receptor leads to influx of sodium and calcium. A muscles contraction (also known as a muscle twitch or simply twitch) occurs when a Muscle fibre generates tension through the action of Actin Sodium (ˈsoʊdiəm is an element which has the symbol Na( Latin natrium, from Arabic natrun) atomic number 11 atomic mass 22 Calcium (ˈkælsiəm is the Chemical element with the symbol Ca and Atomic number 20 Only when the levels of these electrolytes inside the muscle cell is high enough will it contract. Decreased numbers of functioning receptors therefore impairs muscular contraction.
It has recently been realized that a second category of gravis is due to auto-antibodies against the MuSK protein (muscle specific kinase), a tyrosine kinase receptor which is required for the formation of the neuromuscular junction. MuSK (for Muscle Specific Kinase is a Receptor tyrosine kinase important in neuromuscular development A tyrosine kinase is an Enzyme that can transfer a Phosphate group from ATP to a Tyrosine residue in a Protein. A neuromuscular junction ( NMJ) is the Synapse or junction of the Axon terminal of a Motoneuron with the motor end plate, the Antibodies against MuSK inhibit the signaling of MuSK normally induced by its nerve-derived ligand, agrin. Agrin is a large Proteoglycan whose best characterised role is in the development of the Neuromuscular junction during Embryogenesis. The result is a decrease in patency of the neuromuscular junction, and the consequent symptoms of MG.
People treated with penicillamine can develop MG symptoms. Their antibody titer is usually similar to that of MG, but both the symptoms and the titer disappear when drug administration is discontinued.
MG is more common in families with other autoimmune diseases. A familial predisposition is found in 5% of the cases. This is associated with certain genetic variations such as an increased frequency of HLA-B8 and DR3. People with MG suffer from co-existing autoimmune diseases at a higher frequency than members of the general population. Of particular mention is co-existing thyroid disease where episodes of hypothyroidism may precipitate a severe exacerbation. The thyroid is one of the largest Endocrine glands in the body Hypothyroidism is the disease state in humans and animals caused by insufficient production of Thyroid hormone by the Thyroid gland.
Myasthenia can be a difficult diagnosis, as the symptoms can be subtle and hard to distinguish from both normal variants and other neurological disorders.  A thorough physical examination can reveal easy fatiguability, with the weakness improving after rest and worsening again on repeat of the exertion testing. Physical examination or clinical examination is the process by which a Health care provider investigates the body of a Patient for signs Applying ice to weak muscle groups characteristically leads to improvement in strength of those muscles. Ice is a Solid phase, usually crystalline, of a Non-metalic substance that is liquid or gas at Room temperature, such as Ammonia Additional tests are often performed, as mentioned below. Furthermore, a good response to medication can also be considered a sign of autoimmune pathology.
Muscle fatigability can be tested for many muscles. A thorough investigation includes:
If the diagnosis is suspected, serology can be performed in a blood test to identify antibodies against the acetylcholine receptor. Serology is the scientific study of blood serum. In practice the term usually refers to the Diagnostic identification of antibodies in the serum A blood test is a laboratory analysis performed on a Blood sample that is usually extracted from a Vein in the arm using a needle, or via Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily An acetylcholine receptor (abbreviated AChR) is an Integral membrane protein that responds to the binding of the Neurotransmitter Acetylcholine The test has a reasonable sensitivity of 80–96%, but in MG limited to the eye muscles (ocular myasthenia) the test may be negative in up to 50% of the cases. About half of the patients without antibodies against the acetylcholine receptor have antibodies against the MuSK protein. MuSK (for Muscle Specific Kinase is a Receptor tyrosine kinase important in neuromuscular development In specific situations (decreased reflexes which increase on facilitation, co-existing autonomic features, suspected presence of neoplasm, presence of increment or facilitation on repetitive EMG testing) testing is performed for Lambert-Eaton syndrome, in which other antibodies (against a voltage-gated calcium channel) can be found. Lambert-Eaton myasthenic syndrome (LEMS is a rare Autoimmune disorder which affects calcium channels of the nerve-muscle ( neuromuscular) junction A Calcium channel is an Ion channel which displays selective permeabiltiy to Calcium ions
Muscle fibers of patients with MG are easily fatigued, and thus do not respond as well as muscles in healthy individuals to repeated stimulation. By repeatedly stimulating a muscle with electrical impulses, the fatiguability of the muscle can be measured. This is called the repetitive nerve stimulation test. In single fiber electromyography, which is considered to be the most sensitive (although not the most specific) test for MG, a thin needle electrode is inserted into a muscle to record the electric potentials of individual muscle fibers. Electromyography (EMG is a technique for evaluating and recording the activation signal of muscles By finding two muscle fibers belonging to the same motor unit and measuring the temporal variability in their firing patterns (i. e. their 'jitter'), the diagnosis can be made.
The "edrophonium test" is infrequently performed to identify MG; its application is limited to the situation when other investigations do not yield a conclusive diagnosis. This test requires the intravenous administration of edrophonium chloride (Tensilon, Reversol), a drug that blocks the breakdown of acetylcholine by cholinesterase and temporarily increases the levels of acetylcholine at the neuromuscular junction. Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. Edrophonium is a readily reversible Acetylcholinesterase inhibitor. In Biochemistry, cholinesterase is an enzyme that catalyzes the Hydrolysis of the Neurotransmitter Acetylcholine into A neuromuscular junction ( NMJ) is the Synapse or junction of the Axon terminal of a Motoneuron with the motor end plate, the In people with myasthenia gravis involving the eye muscles, edrophonium chloride will briefly relieve weakness.
A chest X-ray is frequently performed; it may point towards alternative diagnoses (e. A chest X-ray, commonly abbreviated CXR, is a projection radiograph ( X-ray) taken by a Radiographer, of the Thorax which is used g. Lambert-Eaton due to a lung tumor) and comorbidity. It may also identify widening of the mediastinum suggestive of thymoma, but computed tomography (CT) or magnetic resonance imaging (MRI) are more sensitive ways to identify thymomas, and are generally done for this reason. The mediastinum is a non-delineated group of structures in the Thorax (chest surrounded by Loose connective tissue. In Medicine ( Oncology) thymoma is a Tumor originating from the Thymus. Computed tomography (CT is a Medical imaging method employing Tomography.
Spirometry (lung function testing) may be performed to assess respiratory function if there are concerns about a patient's ability to breathe adequately. Spirometry (meaning the measuring of breath) is the most common of the Pulmonary Function Tests (PFTs measuring Lung function specifically the measurement The vital capacity (VC) may be monitored at intervals in order not to miss a gradual worsening of muscular weakness. Severe myasthenia may cause respiratory failure due to exhaustion of the respiratory muscles. Respiratory failure is a medical term for inadequate Gas exchange by the Respiratory system.
Immunofluorescence shows IgG antibodies on the neuromuscular junction. Immunofluorescence is the labeling of antibodies or Antigens with fluorescent Dyes This technique is often used to visualize the subcellular Immunoglobulin G ( IgG) is a Monomeric Immunoglobulin, built of two heavy chains γ and two light chains. (Note that it is not the antibody which causes myasthenia gravis that fluoresces, but rather a secondary antibody directed against it. A secondary antibody is an Antibody that binds to Primary antibodies or antibody fragments ) Muscle electron microscopy shows receptor infolding and loss of the tips of the folds, together with widening of the synaptic clefts. Chemical synapses are specialized junctions through which Neurons signal to each other and to non-neuronal cells such as those in Muscles or Glands Both these techniques are currently used for research rather than diagnostically.
The most widely accepted classification of myasthenia gravis is the Myasthenia Gravis Foundation of America Clinical Classification:
Myasthenia Gravis is associated with various autoimmune diseases, including:
Seropositive and "double-seronegative" patients often have thymoma or thymic hyperplasia. Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues The thyroid is one of the largest Endocrine glands in the body Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an Autoimmune disease where the body's own T-cells attack the cells of the Thyroid Graves' disease is a Thyroid disorder characterized by goiter, Exophthalmos, "orange-peel" skin and Hyperthyroidism. Diabetes mellitus type 1 (Type 1 diabetes Type I diabetes T1D T1DM IDDM juvenile diabetes is a form of Diabetes mellitus. Rheumatoid arthritis ( RA) is a chronic systemic autoimmune disorder that causes the Immune system to attack the Joints, where Systemic lupus erythematosus ( SLE or lupus,) is a chronic autoimmune disease that can be fatal though with recent medical advances fatalities are becoming A demyelinating disease is any Disease of the Nervous system in which the Myelin sheath of Neurons is damaged In Medicine ( Oncology) thymoma is a Tumor originating from the Thymus. However, anti-MuSK positive patients do not have evidence of thymus pathology.
Treatment is by medication and/or surgery. Medication consists mainly of cholinesterase inhibitors to directly improve muscle function and immunosuppressant drugs to reduce the autoimmune process. An acetylcholinesterase inhibitor or anti-cholinesterase is a chemical that inhibits the Cholinesterase enzyme from breaking down Acetylcholine For a list of immunosuppressive drugs see the Transplant rejection page. Thymectomy is a surgical method to treat MG. A thymectomy is an operation to remove the Thymus gland. It usually results in remission of Myasthenia gravis with the help of medication including Steroids For emergency treatment, plasmapheresis or IVIG can be used as a temporary measure to remove antibodies from the blood circulation. Plasmapheresis (from the Greek plasma, something molded and apheresis, taking away is the removal treatment and return of (components of Blood Intravenous immunoglobulin (IVIG is a blood product administered Intravenously It contains the pooled IgG Immunoglobulins ( Antibodies
If the myasthenia is serious (myasthenic crisis), plasmapheresis is used to remove the putative antibody from the circulation. Plasmapheresis (from the Greek plasma, something molded and apheresis, taking away is the removal treatment and return of (components of Blood Similarly, intravenous immunoglobulins (IVIG) are used to bind the circulating antibodies. Intravenous immunoglobulin (IVIG is a blood product administered Intravenously It contains the pooled IgG Immunoglobulins ( Antibodies Both of these treatments have relatively short-lived benefits, typically measured in weeks.
Thymectomy, the surgical removal of the thymus, is essential in cases of thymoma in view of the potential neoplastic effects of the tumor. A thymectomy is an operation to remove the Thymus gland. It usually results in remission of Myasthenia gravis with the help of medication including Steroids In Human anatomy, the thymus is an organ located in the upper Anterior portion of the chest cavity just behind the Sternum. In Medicine ( Oncology) thymoma is a Tumor originating from the Thymus. However, the procedure is more controversial in patients who do not show thymic abnormalities. Although some of these patients improve following thymectomy, some patients experience severe exacerbations and the highly controversial concept of "therapeutic thymectomy" for patients with thymus hyperplasia is disputed by many experts and efforts are underway to unequivocally answer this important question.
There are a number of surgical approaches to the removal of the thymus gland: transsternal (through the sternum, or breast bone), transcervical (through a small neck incision), and transthoracic (through one or both sides of the chest). The sternum (from Greek στέρνον sternon, "chest" or breastbone) is a long flat Bone located in the center of the thorax (chest The transsternal approach is most common and uses the same length-wise incision through the sternum (breast bone)used for most open-heart surgery. The transcervical approach is a less invasive procedure that allows for removal of the entire thymus gland through a small neck incision. There has been no difference in success in symptom improvement between the transsternal approach and the minimally invasive transcervical approach. 
Thymoma is relatively rare in younger (<40) patients, but paradoxically especially younger patients with generalized MG without thymoma benefit from thymectomy. Of course, resection is also indicated for those with a thymoma, but it is less likely to improve the MG symptoms.
With treatment, patients have a normal life expectancy, except for those with a malignant thymoma (whose lesser life expectancy is on account of the thymoma itself and is otherwise unrelated to the myasthenia). In Medicine ( Oncology) thymoma is a Tumor originating from the Thymus. Quality of life can vary depending on the severity and the cause. The drugs used to control MG either diminish in effectiveness over time (cholinesterase inhibitors) or cause severe side effects of their own (immunosupressants). In Biochemistry, cholinesterase is an enzyme that catalyzes the Hydrolysis of the Neurotransmitter Acetylcholine into For a list of immunosuppressive drugs see the Transplant rejection page. A small percentage (around 10%) of MG patients are found to have tumors in their thymus glands, in which case a thymectomy is a very effective treatment with long-term remission. In Human anatomy, the thymus is an organ located in the upper Anterior portion of the chest cavity just behind the Sternum. A thymectomy is an operation to remove the Thymus gland. It usually results in remission of Myasthenia gravis with the help of medication including Steroids However, most patients need treatment for the remainder of their lives, and their abilities vary greatly. It should be noted that MG is not usually a progressive disease. The symptoms may come and go, but the symptoms usually do not get worse as the patient ages. For some, the symptoms decrease after a span of 3–5 years.
Myasthenia gravis occurs in all ethnic groups and both genders. It most commonly affects women under 40 - and people from 50 to 70 years old of either sex, but it has been known to occur at any age. Younger patients rarely have thymoma. The prevalence in the United States is estimated at 20 cases per 100,000 in the United States. The United States of America —commonly referred to as the  Risk factors are the female gender with ages 20 – 40, familial myasthenia gravis, D-penicillamine ingestion (drug induced myasthenia), and having other autoimmune diseases.
Three types of myasthenia symptoms in children can be distinguished:
The congenital myasthenias cause muscle weakness and fatigability similar to those of MG. The symptoms of CMS usually begin within the first two years of life, although in a few forms patients can develop their first symptoms as late as the seventh decade of life. A diagnosis of CMS is suggested by the following:
The symptoms of CMS can vary from mild to severe. It is also common for patients with the same form, even members of the same family, to be affected to differing degrees. In most forms of CMS weakness does not progress, and in some forms, the symptoms may diminish as the patient gets older. Only rarely do symptoms of CMS become worse with time.